Design of Chiral NHC‐Carboxylates as Potential Ligands for Pd‐Catalyzed Enantioselective C−H Activation

Abstract

Despite numerous efforts, the synthesis of scalemic carbo-and heterocycles through Pd 0-catalyzed C(sp 3)À H activation employing chiral ancillary ligands or chiral bases is still limited. Inspired by the recently reported outstanding performance of IBiox-type NHC ligands and bifunctional ligands in similar transformations, a new class of bifunctional NHC-ligands bearing a pendant carboxylate group was designed. A library of 10 imidazolium-carboxylic acids was obtained in five to six steps from enantiopure L-tert-leucinol. In addition, four well-defined Pd(DMBPA)-NHC palladacycles were synthesized in good to excellent yields from the corresponding imidazolium precursors. These complexes were tested in a prototypical C(sp 3)À H arylation reaction, and the most active one afforded the indoline product in low yield but significant enantioselectivity. These new bifunctional NHCs could find broader applications in catalytic enantioselective transformations occurring under milder conditions.

Palladium(ii)/N-heterocyclic carbene (NHC) catalyzed direct C–H arylation of heteroarenes with different aryl bromides and chlorides

“…First, the 2-acetylfuran was coupled with several aryl bromides in the presence of the Pd-PEPPSI complexes (3a-e). Complete conversion was obtained when 4-bromobenzaldehyde and 4-bromoacetophenone were used, with 73-95% yields (Table 3, entries [28][29][30][31][32][33][34][35][36][37][38][39][40][42][43][44][45]. Good conversions were obtained with the rest of the aryl bromides using all the complexes except the reaction with 4-bromotoluene in the presence of 3a catalyst, which showed 79% conversion (Table 3, entry 1).…”

“…These catalysts work as oxidants. Plentiful N-heterocyclic carbene catalysts based on various metal complexes, such as Pd, 27,28 Pt, 29 Rh, 30 Ir, 31 Ru, 32 Co, 33 Fe, 34 Ni, 35 Cu, 36 Ag, 37 and Au, 38 have been used for the C–H bond functionalization reaction. Although palladium NHC complexes have strong electron donor and flexible steric bulkiness properties compared to phosphine and N-donor ligands, they also have hydrolytic instability, due to which their application in cross-coupling reactions has not been prominent.…”